Criteria for the establishment of new systems and antigens

Criteria for the establishment of new blood group systems

For one or more antigen(s) to form a new blood group system:

• The antigen(s) in the system must be found on erythrocytes (see footnote 1 + 2 below)
• The antigen(s) must be defined by human antibodies that are neither autoantibodies nor exist only as monoclonal antibodies, i.e. these antibodies have been made by at least one individual lacking the antigen in question.
• The antigen(s) must be (an) inherited character(s).
• The gene encoding the antigen(s) must have been identified and sequenced. 
• The gene must be different from, and not a closely-linked homologue of, all other genes encoding antigens of existing blood group systems.

Footnotes 

1. If the antigen is difficult to detect by standard hemagglutination on erythrocytes, the WP may take into consideration if it can be detected by alternative methods (e.g. flow cytometry or mass spectrometry) and make decisions about each antigen candidate given the whole body of evidence presented.
    
2. The WP may also take into consideration if the antigen can be detected on reticulocytes and/or other earlier erythroid cell stages, and possibly also the clinical consequences thereof (e.g. if the antigen/antibodies in question result in pathologies often associated with other blood groups).

Criteria for assignment of a new blood group antigen

• The antigen must be found on erythrocytes (see footnote 1 + 2 below)
• The antigen must be defined by human antibodies that are neither autoantibodies nor exist only as monoclonal antibodies, i.e. these antibodies have been made by at least one individual lacking the antigen in question.
• An antigen must be inherited.
  Inheritance can be shown either according to pedigree following a family study, or, if a family study has not been performed, by reporting at least two unrelated probands with the same serological phenotype.
  If the new antigen belongs to a known system, the corresponding genetic change needs to be shown.

       At least one of the following four criteria must also be met:

• An antithetical relationship is shown between a new antigen and one (or more) already assigned.
• Expression of the antigen is associated with a variation in the nucleotide sequence of a gene controlling a preexisting system. Causal proof (e.g. by knock-in or knock-down/knock-out experiments in cell lines) is preferred but may not be necessary if the WP deems the association data sufficient.
• Evidence, from a linkage analysis of family data, that the implicated allele is very likely to be a newly recognised form of the gene in question, thereby supporting serological and/or biochemical information.
• Demonstration that an antigen is located on a protein, glycoprotein or lipoprotein that carries other antigens belonging to a preexisting system.  

Footnotes 

1. If the antigen is difficult to detect by standard hemagglutination on erythrocytes, the WP may take into consideration if it can be detected by alternative methods (e.g. flow cytometry or mass spectrometry) and make decisions about each antigen candidate given the whole body of evidence presented.
    
2. The WP may also take into consideration if the antigen can be detected on reticulocytes and/or other earlier erythroid cell stages, and possibly also the clinical consequences thereof (e.g. if the antigen/antibodies in question result in pathologies often associated with other blood groups).

Criteria for establishment of a blood group collection

A collection must contain two or more antigens that are related serologically, biochemically, or genetically, but which do not fit the criteria required for system status.

Criteria for inclusion in the 700 series 

1. Incidence of <1% in most populations tested.
2. Distinction from all other numbered low incidence antigens of the 700 series as well as those of the blood group systems and collections.
3. Demonstration of inheritance through at least 2 generations.

Criteria for inclusion in the 901 series

1. Incidence of >90% in most populations tested.
2. Distinction from all other numbered high incidence specificities.
3. Demonstration that the antigen is lacking from the red cells of at least 2 siblings, i.e. that the negative phenotype is genetically determined.

Obsolete Numbers

Once a number has been allocated to a specificity, that number cannot be subsequently used for any other specificity. Consequently, if the number of a specificity becomes inappropriate, then that number becomes obsolete. The obsolete numbers are listed here.